Researchers are exploring exciting lines of evidence suggesting that depression is not simply an imbalance of neurochemicals in the brain but possibly fallout from an inflammatory response mounted by the body to deal with stress.

Investigators at the Icahn School of Medicine at Mount Sinai, in New York City, recently linked differences in the peripheral immune system in a mouse model to susceptibility to social stress, findings they correlated with serum cytokine levels in patients with treatment-resistant depression. Other experts go a step further and promote the idea that the inflammatory state underlying depression may be caused by a pathogen such as a parasite, bacterium, or virus. This evolving research thrust could have huge implications for depression treatment. It could change an almost totally symptom-based paradigm into one based more on biology.

Biology-Based Diagnosis

“It means that clinicians should start diagnosing based on biology and not on behavioural symptoms,” said Scott Russo, PhD, associate professor of neuroscience, Icahn School of Medicine at Mount Sinai, told Medscape Medical News. Dr Russo led the research team that carried out the mouse experiments, the results of which were published online October 20 in the Proceedings of the National Academy of Sciences. After drawing blood from experimental mice and checking for levels of interleukin 6 (IL-6), researchers put the rodents separately into the cage of a larger, more aggressive mouse, allowing physical contact for 10 minutes a day for 10 days.

Some mice showed symptoms similar to those found in depressed patients, such as social avoidance. “The mice also no longer preferred sugar water and didn’t want to have sex, and it took more to stimulate them in terms of the pleasure centers in the brain,” first author of the article, Georgia Hodes, PhD, postdoctoral researcher in neuroscience, Icahn School of Medicine, told Medscape Medical News. “These animals were in a state that seems to be somewhat similar to depression.”

What separated these mice from those that did not develop these symptoms were differences in the peripheral immune system. Even before they were put into the stressful situation, these susceptible mice had more white blood cells than those that were resilient.”When we stimulated those white blood cells, they released more IL-6, and it predicted which animals would go on to become susceptible and which would go on to become resilient,” said Dr Hodes. had more white blood cells than those that were resilient.